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Microarray analysis of gene expression in 3-methylcholanthrene-treated human endothelial cells
Park, Hye Rim,Yang, Hana,Kim, Gun-Dong,Son, Gun Woo,Park, Yong Seek 대한독성유전단백체학회 2014 Molecular & cellular toxicology Vol.10 No.1
Cigarette smoke has many toxic components that can lead to the disruption of various cellular processes. Increase in oxidative stress due to cigarette smoke causes production of reactive oxygen species, which induce vascular disease. 3-methylcholanthrene (3MC) is an environmental contaminant derived from the incomplete combustion of cigarette smoke and is one of the major polycyclic aromatic hydrocarbons. 3MC activates the aryl hydrocarbon receptor and contributes to carcinogenesis and vascular disease. The present study investigated gene expression in 3MC-treated human umbilical vein endothelial cells by microarray gene expression profiling. We found 1,279 and 717 genes with altered gene expression within 24 h of 100 nM and $1{\mu}m$ 3MC treatment, respectively; these genes were distributed into distinct functional groups. Some of the genes including ICAM1, PTGS2, APOL3, and GPX-1, were related to cardiovascular disease. Our results support the hypothesis that 3MC-stimulated gene expression in endothelial cells may play a role in the development of cardiovascular disease.
Kim, Jong Woo,Kang, Won Sub,Lee, Sang Min,Kim, Su Kang,Park, Hae Jeong,Gwak, Geum-Hee,Baik, Hyung Hwan 대한독성유전단백체학회 2012 Molecular & cellular toxicology Vol.8 No.3
Extracellular matrix (ECM) abnormality is implicated in the pathogenesis of schizophrenia. Matrix metalloproteinases (MMPs) mediate the proteolysis of ECM and may play a crucial role in neuronal plasticity. We investigated whether single nucleotide polymorphisms (SNPs) of MMP1 and MMP8 are associated with the development of schizophrenia. We also assessed the relationships between MMP1, MMP8 SNPs and the core symptoms of schizophrenia such as persecutory delusion, auditory hallucinations, affective disturbances, and poor concentration according to the Operation Criteria Checklist for Psychotic Illness (OPCRIT). Three coding SNPs (rs470558, Ala216Ala in MMP1; rs3740938, Leu291Leu and rs1940475, Lys87Glu in MMP8) were selected, and 263 patients and 283 controls were evaluated. SNPStats was used to obtain the odds ratio (OR), 95% confidence intervals (CI), and P value adjusted for age and gender as covariables. Multiple logistic regression models (codominant1, codominant2, dominant, recessive, and log-additive) were employed to analyze genetic data. As a result, the three examined SNPs were not associated with the development of schizophrenia. In the analysis of clinical symptoms, the genotype frequency of rs470558 in MMP1 was associated with auditory hallucinations (P=0.04 in the codominant1 model, P=0.014 in the dominant1 model, and P=0.0066 in the log-additive model). The allele frequency of rs470558 also showed a significant difference between schizophrenia without auditory hallucinations [the auditory hallucination (-) group] and schizophrenia with auditory hallucinations [the auditory hallucination (+) group] (P=0.009, OR=1.94, 95% CI=1.19-3.28). The A allele frequency of rs470558 was higher in the auditory hallucination (+) group (19.2%) than that in the auditory hallucination (-) group (10.8%). Two MMP8 SNPs (rs3740938 and rs1940475) were not associated with the development and core symptoms of schizophrenia, respectively. These results suggest that the A allele of rs470558 (Ala216Ala) in MMP1 may contribute to the susceptibility to auditory hallucinations of schizophrenia.
Biological safety and B cells activation effects of Zanthoxylum schinifolium
Park, Dae-Hun,Park, Yong-Il,Li, Yong-Chun,Xu, Hong De,Lee, Jong-Hwa,Kim, Young-Jin,Jang, Soon-Ae,Park, Sung-Jin,Lee, Yun-Lyul,Ahn, Jae-Bum,Cho, Soon-Chang,Lee, Min-Jae 대한독성유전단백체학회 2011 Molecular & cellular toxicology Vol.7 No.2
Zanthoxylum schinifolium has been used as culinary applications in Asia and some of its elements have been elucidated to have various pharmaceutical effects such as anti-platelet aggregation, inhibitory activities against monoamine oxidase, antioxidant and anticancer activities, and anti-inflammatory activity. In this study 21-day repeated Zanthoxylum schinifolium oral administration (250 mg/kg/day, once a day) modulated B cell-related immunity and biologically safe. After 21-day repeated oral administration, the expression of CD19 bound cells was significantly increased compared to those of the other surface molecules and the percentages of Alamar $Blue^{(R)}$ reduction were in LPS-treated splenocytes higher than in no treated but it was not different with in Con A-treated splenocytes and in no treated. Twenty-one-day repeated Z. schinifolium administration could not change the index of biological safety such as CBC, hematological enzymes, and especially histopathological morphologies. From the results Z. schinifolium-repeated administration enhances B cell immunity and is biological safe. Conclusively Z. schinifolium is one of the safe candidates to modulate immunity.
Identification of estrogenic genes responding to phthalate esters treatment in human MCF-7 cells
Kim, Youn-Jung,Kim, Eun-Young,Ryu, Jae-Chun 대한독성유전단백체학회 2011 Molecular & cellular toxicology Vol.7 No.2
The phthalate esters represent a class of chemicals used widely and diversely in industries as a plasticizer for elasticity and adhesion. Some phthalate diesters are classified as endocrine disrupting chemicals (EDCs), because they have been found weakly estrogenic. This study aimed to identify the changes of gene expression profiles by BBP, DBP, and DEHP using cDNA microarray. Firstly, we have selected the MCF-7 cell line, mainly used to estrogenic related research and selected the doses appearing the highest estrogenicity in E-screen assay to examine the estrogenicity and gene expression profiles of phthalate esters. Total RNA was isolated from cells treated with each phthalate esters (BBP, DBP, and DEHP) and $17{\beta}$-estradiol, and then changes of gene expression were analyzed using cDNA microarray (KISTCHIP-400). This microarray includes 416 endocrine related genes based on public database and research papers. For the microarray analysis, genes that showed a 1.5-fold or greater change in their expression level (increase or decrease) were detected as differentially expressed genes (DEGs). Of the 416 genes analyzed, 95, 26, and 63 genes were identified showing significant changes in gene expression resulting from BBP, DBP, and DEHP, respectively. Among these genes, 11 genes, including MGP, SEPP1, and BAK1 were induced by more than 2 of 3 phthalate esters compared with $17{\beta}$-estradiol. Therefore, it suggests that these genes may be associated with estrogenic effect of the phthalate esters on transcriptional level.
The effects of benzene and toluene on leukotactin-1-induced migration of EoL-1 cells
Song, Bo-Bae,Yang, Eun-Ju,Kim, Bo-Mi,Lee, Ji-Sook,Yun, Chi-Young,Im, Yang-Bin,Kim, In-Sik 대한독성유전단백체학회 2011 Molecular & cellular toxicology Vol.7 No.2
Benzene and toluene are volatile organic compounds (VOCs) that are produced from various building materials and may lead to sick building syndrome. In addition, these materials exert cytotoxic and carcinogenic effects in immune cells. To understand the effects of VOCs on immunological regulation, we investigated the effects of VOCs on cell migration in response to CC chemokines such as leukotactin-1 (Lkn -1), monocyte chemoattractant protein-1 (MCP-1), eotaxin, $MIP-1{\alpha}$ and RANTES in human eosinophilic leukemia EoL-1 cells. VOCs exerted no cytotoxicity against EoL-1 cells at concentrations ranging from $0.1\;{\mu}M$ to $50\;{\mu}M$. A chemotaxis assay was conducted to evaluate the cell movement. The assay revealed that benzene and toluene differentially increased the migration of EoL-1 cells in response to Lkn-1, but not MCP-1, eotaxin, $MIP-1{\alpha}$ or RANTES. The expression of CCR1 and CCR3 binding to Lkn-1 were not altered by benzene and toluene. Additionally, the increased cell migration due to benzene and toluene was inhibited by PD98059, SB202190 and SP600125. Benzene and toluene also induced the phosphorylation of ERK, p38 mitogen-activated protein kinase (p38 MAPK) and JNK in a time-dependent manner. Overall, benzene and toluene influenced Lkn-1-induced migration of human eosinophilic cells via activation of MAPKs. These results suggest that benzene and toluene play a role as risk factors in the regulation of immune response. Furthermore, these findings provide a role for VOCs in the immunological processes involved in indoor air pollution-induced diseases.
Mercury exposure and color vision loss of some Koreans in a fishery area
Kim, Dae-Seon,Kwon, Young Min,Chung, Hee-Ung,Choi, Kyung Hee,Oh, Hyun Jin,Lee, Eun-Hee 대한독성유전단백체학회 2012 Molecular & cellular toxicology Vol.8 No.4
This study was conducted to evaluate the relationship between exposure to mercury and color vision loss in populations located within fishery areas in South Korea. From a total of 511 subjects, 401 were assessed for acquired color vision loss. Subjects determined to have congenital loss or subjects with visual acuity less than 0.6 were excluded from the study. Mercury concentrations were analyzed in blood, urine, and hair samples. The Ishihara test was used to assess congenital color vision loss, and the Lanthony test was used for acquired color vision loss. Acquired color vision loss was present in 56 (14%) of the subjects and 345 (86%) subjects were normal. The geometric means of mercury concentration were 3.78 ${\mu}g/L$ in blood, 0.64 ${\mu}g/g$ creatinine in urine, and 1.16 ${\mu}g/g$ in hair. Although mercury was identified in relatively low concentrations, mercury concentrations in subjects with acquired color vision loss were higher than that of normal subjects. The frequency of color vision loss in subjects with higher mercury concentrations was increased compared to subjects with lower mercury concentrations. The color confusion index increased with increasing mercury levels. This study suggests that exposure to low levels of mercury affects color vision loss as an early marker of neurotoxic damage in humans.
A safety assessment of phototoxicity and sensitization of $SiO_2$ nanoparticles
Choi, Jae-Eun,Park, Yoon-Hee,Lee, Eun-Young,Jeong, Sang-Hoon,Kim, Sun-Yae,Kim, Meyoung-Kon,Son, Sang-Wook 대한독성유전단백체학회 2011 Molecular & cellular toxicology Vol.7 No.2
Despite widespread use of silicon dioxide ($SiO_2$) NPs in industry and in our daily lives, no studies so far have evaluated the potential of their skin phototoxicity and sensitization. This study was designed to investigate the potential of phototoxicity and sensitization of $SiO_2$ NPs. Assessment of the potential of skin phototoxicity was carried out using the 3T3 neutral red uptake test, an HSEM, and an animal model. The potential of skin sensitization was evaluated by a non-radioisotope local lymph node assay (non-RI LLNA). Findings from the present study suggest that the HSEM may be a reasonable model system for evaluation of skin phototoxicity of NPs. In addition, our data demonstrate that non-RI LLNA may be a useful method for identification of skin sensitization of NPs. In this study, we showed that $SiO_2$ NPs do not induce phototoxicity or skin sensitization.
Cisplatin induced nephrotoxicity is inhibited by Taxilli Ramulus
Lee, Gihyun,Lee, Jun-Ho,Ham, Kyoung Keun,Lee, Hyojung,Kim, Hyunseong,Lee, Hyeonhoon,Hong, Moochang,Shin, Minkyu,Bae, Hyunsu 대한독성유전단백체학회 2012 Molecular & cellular toxicology Vol.10 No.2
Taxilli Ramulus has been shown have antioxidant and anti-inflammatory activities. Cisplatin is the most active cytotoxic anti-cancer drugs. However, the nephrotoxicity of cisplatin limits its use as a therapeutic. In the present study, we examined whether Taxilli Ramulus could protect against cisplatin induced acute renal failure in mice. Taxilli Ramulus were administrated orally once a day for 3 days (150 or 300 mg/kg body wt). After 3 days, all groups of mice received a single dose of cisplatin (25 mg/kg (body wt)) intraperitoneally. Taxilli Ramulus treatment ameliorated renal dysfunction 72 h after cisplatin injection. Taxilli Ramulus treated group had significantly reduced levels of proinflammatory cytokines when compared to the control group. These results show that Taxilli Ramulus is a potent herbal medicine that can reduce cisplatin nephrotoxicity. It also demonstrates that Taxilli Ramulus can prevent the renal toxic effects caused by cisplatin.
Kwon, Jung-Taek,Kim, Hyun-Mi,Kim, Pilje,Choi, Kyunghee 대한독성유전단백체학회 2014 Molecular & cellular toxicology Vol.10 No.1
Didecyldimethylammonium chloride (DDAC) is a commonly used biocide that can cause lung inflammation and fibrosis. However, the mechanism of this pulmonary toxicity is unclear. Thus, we examined the mechanism for the DDAC-induced pulmonary toxicity at the cellular level by using lung epithelial cells. DDAC induced cell damage, including injury of mitochondria and lysosomes with the release of lactate dehydrogenase (LDH), as well as caused cell morphological changes and necrotic reactions. In a clonogenic assay, treatment with a low concentration of DDAC ($5{\mu}m$) for 10 days reduced both the number and size of the colonies, which are indexes of cell growth. In addition, DDAC increased intracellular reactive oxygen species (ROS) production while it decreased glutathione (GSH) activity. Therefore, our results suggest that exposure to even a low concentration of DDAC may inhibit cell growth and cause oxidative stress in lung epithelial cells.
Implication of ultraviolet B radiation exposure for non-melanoma skin cancer in Korea
Lee, Sang Geun,Yoon, Hong Seok,Bae, Hyunjoo,Ha, Jongsik,Pak, Haeyong,Shin, Yongseung,Son, Sang Wook 대한독성유전단백체학회 2014 Molecular & cellular toxicology Vol.10 No.1
Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the two most common subtypes of non-melanoma skin cancer (NMSC). Ultraviolet B radiation (UVB) exposure has been correlated with the occurrence of NMSC in humans. Thus far, studies investigating UVB-associated risk factors for NMSC in Asia have not been completed. The goal of this study was to evaluate the impact of UVB radiation exposure on the incidence of NMSC. Using UVB index and National Health Insurance databases, we performed a regression analysis using a linear model to describe the relationship between UVB measurements and NMSC incidence. The cut-off age at which the number of NMSC patients increased significantly was 60 years old. Our study found that 52.2% of NMSC patients were males, while 47.8% were females. There was a strong positive correlation between the annual UVB index and NMSC incidence rates in individuals 60 years and older. Males, individuals 60 years and older and persons who live in higher UVB index in Korea might be susceptible to NMSC.